title: Safety and infectivity of two doses of live-attenuated recombinant cold-passaged human parainfluenza type 3 virus vaccine rHPIV3cp45 in HPIV3-seronegative young children.
abstract: BACKGROUND
  Human parainfluenza virus type 3 (HPIV3) is a common cause of upper and lower respiratory tract illness in infants and young children. Live-attenuated cold-adapted HPIV3 vaccines have been evaluated in infants but a suitable interval for administration of a second dose of vaccine has not been defined.
  
  
  METHODS
  HPIV3-seronegative children between the ages of 6 and 36 months were randomized 2:1 in a blinded study to receive two doses of 10⁵ TCID₅₀ (50% tissue culture infectious dose) of live-attenuated, recombinant cold-passaged human PIV3 vaccine (rHPIV3cp45) or placebo 6 months apart. Serum antibody levels were assessed prior to and approximately 4-6 weeks after each dose. Vaccine virus infectivity, defined as detection of vaccine-HPIV3 in nasal wash and/or a≥4-fold rise in serum antibody titer, and reactogenicity were assessed on days 3, 7, and 14 following immunization.
  
  
  RESULTS
  Forty HPIV3-seronegative children (median age 13 months; range 6-35 months) were enrolled; 27 (68%) received vaccine and 13 (32%) received placebo. Infectivity was detected in 25 (96%) of 26 evaluable vaccinees following doses 1 and 9 of 26 subject (35%) following dose 2. Among those who shed virus, the median duration of viral shedding was 12 days (range 6-15 days) after dose 1 and 6 days (range 3-8 days) after dose 2, with a mean peak log₁₀ viral titer of 3.4 PFU/mL (SD: 1.0) after dose 1 compared to 1.5 PFU/mL (SD: 0.92) after dose 2. Overall, reactogenicity was mild, with no difference in rates of fever and upper respiratory infection symptoms between vaccine and placebo groups.
  
  
  CONCLUSIONS
  rHPIV3cp45 was immunogenic and well-tolerated in seronegative young children. A second dose administered 6 months after the initial dose was restricted in those previously infected with vaccine virus; however, the second dose boosted antibody responses and induced antibody responses in two previously uninfected children.
authors.affiliation: Seattle Children's Hospital, University of Washington, 4800 Sand Point Way NE, Seattle, WA 98105, United States. Electronic address: janet.englund@seattlechildrens.org.
authors.forename: Janet A
authors.initials: JA
authors.lastname: Englund
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Karron
authors.forename: Coleen K
authors.initials: CK
authors.lastname: Cunningham
authors.forename: Philip
authors.initials: P
authors.lastname: Larussa
authors.forename: Ann
authors.initials: A
authors.lastname: Melvin
authors.forename: Ram
authors.initials: R
authors.lastname: Yogev
authors.forename: Ed
authors.initials: E
authors.lastname: Handelsman
authors.forename: George K
authors.initials: GK
authors.lastname: Siberry
authors.forename: Bhavanji
authors.initials: B
authors.lastname: Thumar
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Schappell
authors.forename: Catherine V
authors.initials: CV
authors.lastname: Bull
authors.forename: Helen Y
authors.initials: HY
authors.lastname: Chu
authors.forename: Anne
authors.initials: A
authors.lastname: Schaap-Nutt
authors.forename: Ursula
authors.initials: U
authors.lastname: Buchholz
authors.forename: Peter L
authors.initials: PL
authors.lastname: Collins
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Schmidt
mesh_terms: D000914:Antibodies, Viral / Q000097:blood; D002675:Child, Preschool; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009296:Nasal Cavity / Q000821:virology; D022241:Parainfluenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000235:genetics / Q000276:immunology*; D010224:Parainfluenza Virus 3, Human / Q000235:genetics / Q000276:immunology*; D010919:Placebos / Q000008:administration & dosage; D010253:Respirovirus Infections / Q000517:prevention & control* / Q000821:virology; D014611:Vaccination / Q000009:adverse effects* / Q000379:methods*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D022241:Parainfluenza Vaccines; D010919:Placebos; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic
keywords: Live-attenuated vaccine; Parainfluenza; Pediatric vaccine; Recombinant virus vaccine